Cytotoxic T lymphocytes are restricted in their killing function by products of the major histocompatibility complex (H-2 in mice). Mice of (H-2d x H-2b) genotype immunized with foreign antigen (X) have two pools of cytotoxic cells, one specific for X-plus-H-2d and another specific for X-plus-H-2b. H-2k or H-2s cells which carry X are not lysed. We are investigating in a funtional way the receptors on T cells, asking whether they have anti-self H-2 receptors and what are the requirements for inducing T cells. (H-2d x H-2b) T cells which have matured from stem cells in an H-2d environment kill X-plus-H-2d targets better than X-plus-H-2b targets. This "learning" of self-H-2 type will be investigated by transplanting homozygous thymus grafts to H-2 heterozygous T cell deficient mice. Using antigens under Ir gene control and by studying fine specificity markers we will investigate whether the H-2 antigens present during T cell differentiation have a gross effect of the T cell repertoire (i.e. their range of antigen receptors). Using non-H-2 coded alloantigens we intend to study if such antigens can be processed and presented to T cells by specialized cells. We have evidence this happens in vivo but so far no one has demonstrated this type of antigen presentation to cytotoxic cells in vitro.